4b-methyl dodecahydrophenanthrenes and preparation thereof



United States Patent O 4b-METHYL DODECAHYDROPHENLANTHRENES ANDPREPARATION THEREOF Glen E. Artl'r, Cranford, George I. Poos, NorthPlainfield, and Lewis H. Sarett, Princeton, N. J., assignors to Merck &Co., Inc., Rahway, N. J., a corporation of New Jersey No Drawing.Application June 14, 1952, Serial No. 293,672

16 Claims. (or. 260-3403) This invention is concerned with novelpolyhydrophenanthrene compounds, and processes for preparing the same;more particularly it relates to lb-methyl- ,2, ,4 ,4 .7.9,10,10adodecahy rophenanthr ne 1,4,7-trione, derivatives thereof, and processesfior ob.- taining the same.

This application is a continuation-in-part of our. copendingapplication, Serial No. 263,015, filed December 22, 1951, now abandoned.

The novel 4b-methyl dodecahyd'rophenanthrene compounds of our inventionof the formula,

and derivatives thereof, are useful in the total synthesis of steroidcompounds and in the preparation of other valuable polyhydrophenanthrenecompounds. These novel compounds have three fused carbon ringscorresponding to rings A, B, and C of steroidal compounds, and anangular methyl group at position 4b corresponding to the angular methylgroup at position in various steroids.

It is an object of our invention to provide 4b-methyl-1,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydrophenanthrene 1,4,7-trionecompounds and derivatives thereof. It is a further object to provideprocesses for preparing these new compounds from4b-methyl-1,2,3,4,4a,4b,5,6,7,9,10, 10a dodecahydrophenanthrene 1,4 diol7 one (I). Other objects will be apparent from the detailed descriptionhereinafter provided.

In accordance with one embodiment of our invention, we have found thatone stereoisomeric form of the product 4b methyl1,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydrophenanethrene-1,4,7-trione (X[)can be prepared by the following reactions:

wherein R is a substitutent convertible, to a keto substituent byhydrolysis.

In this, process, the 7-keto substituent of the starting material,Compound I, is first blocked or protected by forming a suitable.derivative, such as an enol ether or preferably a ketal, which can bereadily hydrolyzed to obtain the starting compound. This derivative ofCompound I is then oxidized to, convert the hydroxy substituents to ketogroups, and the resulting oxidized product can be hydrolyzed toobtainCompound XI. In the preparation of the ketal derivative the double bondshifts from the 8,8a position to the 8a,9 position. Hydroylsis of theketal derivative to the 7-keto compound results in the shifting of thedouble bond again, and it returns to the 8,8a position.

In our preferred method of carrying out this process, Compound I isfirst converted to the corresponding 7-ethylenedioxy derivative, andthis compound is then oxidized and finally hydrolyzed to obtain CompoundXI as follows:

5 a EZQ The derivative, 4b methyl 7 ethylenedioxy 1, 2, 3,4,4a, 4b,5',6,7,8,10,10a dodecahydrophenanthrene 1,4 diol (VIII), is readilyprepared by heating Compound I with glycol in the presence of an acidcatalyst, such as p-toluene, sulfonic acid. The reaction is preferablycarried out in a suitable inert solvent medium, for example, ethylenedichloride. It is conveniently effected by heating a mixture of CompoundI, glycol, ethylene. dichloride and p-toluene, sulfonic acid, anddistilling 01f the water of reaction formed as an ethylene dichlorideazeotrope. Upon completion of the reaction, the ethylenedioxy derivativeof Compound I, Compound VIII, is recovered by evaporating the solutionand crystallizing the product from a suitable solvent such as acetone.

Compound VIII can then be, treated with an oxidizing agent to oxidizethe hydroxy groups to keto substituents, and form4b-methyl-7-ethylenedioxy-1,2,3,4,4a,4b,5,6,7,8,-10,10a-dodecahydrophenanthrene-1,4-dione. Thus Compound VIII can beoxidized by reaction with a metal alkoxide in the presence of a suitableketone. We have found that this oxidation step is most readily carriedout in the presence of an inert organic solvent (inter alia, benzene,toluene, dioxane, and the like). The reaction is conveniently effectedby dissolving Compound VIII in a mixture of a ketone and the organicsolvent, adding a metal alkoxide thereto and warming the reactionmixture. Suitable ketones which may be used in this reaction includeacetone, methyl ethyl ketone, cyclohexanone, benzil and p-benzoquinone.We have found that the reaction is most conveniently effected usingcyclohexanone as the ketone, benzene as the inert solvent and aluminumisopropoxide as the metal alkoxide. After the reaction is complete, theoxidized product can be recovered by adding water to the reactionmixture, filtering to remove the precipitated metal hydroxide,concentrating the filtrate to dryness, triturating the residue withpetroleum ether, and recovering Compound X from this solvent.Alternatively, Compound VIII can be oxidized to Compound X by reactingit with pyridine-chromium trioxide complex in a pyridine medium. Afterthe oxidation is complete, Compound X is obtained by diluting thereaction mixture with water, extracting with a mixture of benzene andether, concentrating to dryness, chromatographing the residue soobtained over alkaline alumina, and eluting the product from the aluminawith benzene.

When Compound VIII is oxidized in accordance with the proceduresdescribed above, there is also obtained along with Compound X, theincompletely oxidized compounds,4b-methyl-7-ethylenedioxy-l,2,3,4,4a,4b,5,6,7,8,-l0,10a-dodecahydrophenanthrene-l-one-4-ol (IX), and 4bmethyl 7ethylenedioxy1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-1-ol-4-one (XVII)having the formulas o OH O I E These compounds may be oxidized furtherby the processes described above to obtain Compound X. Alternatively,the compounds may first be hydrolyzed with acid to convert the7-ethylene-dioxy substituent to a keto group, and the resulting diketocompound can then be oxidized to obtain Compound XI. Thus, in accordancewith this embodiment of our invention, Compound XVII may be converted toCompound XI by the following Pursuant to this process, Compound XVII isfirst hydrolyzed by heating with acid to obtain 4b-methyl-1,2,3,-4,4a,4b,5,6,7,9,1 0,10a-dodecahydrophenanthrene-l-o1-4,7- dione (XXI).The latter compound on treatment with chromium trioxide is oxidized toobtain 4b-methyl-l,2,3,- 4,4a,4b,5,6,7,9,l0,10a dodecahydrophenanthrene1,4,7- trione ()OHI) which is a stereoisomeric modification of CompoundXI melting at about 164l66 C. Compound XXII on treatment with a base,such as alkaline alumina, is converted to the stereoisomeric form,Compound XI, melting at about 117-1 17.5 C.

In the process of oxidizing Compound VIII with a metal alkoxide in thepresence of a ketone described above, an inversion at the B/ C ringjunction occurs resulting in the formation of Compounds X and IX whichhave a different B/C ring junction than that of Compound VIII. Thus,

Compound IX is converted to Compound XI following process:

tifi he? by the Compound IX is treated with pyridine-chromium trioxidecomplex in pyridine solution, as described above, to obtain Compound X,which on hydrolysis with acid is converted to Compound XI.

In accordance with a further embodiment of our invention,4b-methyl-7-ethylenedioxyl,2,3,4,4a,4b,5, 6,7,8,10,-10a-dodecahydrophenanthrene-l,4-dione (XX), a stereoisomericmodification of Compound X, is obtained by the following process:

rfi t: M

XIX

(Stereoisomer of XVII) In this process Compound VIII is firstselectively acetylated, for example, by reacting a pyridine solution ofVIII with acetic anhydride, to form4b-methyl-7-ethylenedioxyl,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene- 1,4-diol-l-acetate (XV). The latter compound isthen treated with an oxidizing agent such as pyridine-chromium trioxideto obtain 4b-methyl-7-ethylenedioxy-l,2,3,4,4a.-4b,5,6,7,8,10,10a-dodecahydrophenanthrene-l-o1-4-one-lacetate (XVI)which is readily converted to the corresponding l-hydroxy compound (XIX)by hydrolysis with an alkali such as potassium carbonate.

In this process of hydrolyzing Compound XVI, we have found that eitherCompound XVII or a stcreoisomeric form thereof, namely, Compound XIX, isproduced depending upon the particular conditions under which thehydrolysis is etfected. Under relatively mild conditions employingmoderate amounts of potassium carbonate Compound XVII results, whilewhen a larger OAc quantity of potassium carbonate and/or more strenuousconditions such asv a. prolonged reaction period, are. used, thestereoisomeric. form, Compound XIX, is obtained. This Compound XIXapparently has adifferent B/C ringconfiguration than that. of. CompoundXVII.

When Compound XIX is oxidized further, for example, by treatment withpyridine-chromium trioxide complex,4b-methyl-7-ethylenedioxy-1,2,3,4,4a,4b,5,6,1,,8,10,-a-dodecahydrophenanthrene-1,4-dione (XX), a. stereo.- isomer of X, isobtained. This stereoisomer, Compound XX, is. found to melt at about171-172 C. in. contrast. to Compound X which exhibits a melting. pointof about 120121 C. On hydrolyzing Compound XX. with acid, there isobtained a stereoisomeric form of 4bmethyl1,2,3,4,4a,4b,5,.6,7,9,,10,.10a dodecahydrophenanthrene-l,4,7-trionewhich is different. from Compounds XI and XXII which have been.-described above.

It will be readily apparent to those skilled in the art. that. in placeof utilizing Compound VIII in this syn thesis, other suitablederivatives wherein the 7-keto group is protected by the formation ofother ketals or enol ether derivatives can be used; Similarly, in placeof using acetic anhydride as the acylating agent, other acylating agentsmay also be employed.

Compound I, utilized as. the starting, material in the presentinvention, is a new compound which may be prepared by reacting; 5-methylperhydronaphth-alene1,4- diol-6-one with methyl vinyl ketone in thepresence of an alkaline condensing agent, such as a strong base (interalia, an alkali metal hydroxide. and the like). This. process isdescribed in copending application Serial No. 228,126,. filed May 24,1951, now U. S. Patent 2,617,828.

The 5-methyl-perhydronaphthalene-I,4-diol-6-one used as the startingmaterial in the preparation of Compound I is. prepared as follows:

fl-Ethoxy-propionaldehyde. is reacted with ethyl magnesium bromide toproduce 1-ethoxy-3 -hydroxy-pentane which is oxidized with chromic acidto form 1-ethoxy- 3-keto pentane, the latter compound is treated withethyl ortho-formate and ethanol in the presence of hydrogen chloride toproduce 1,3,3-triethoxy-pentane which upon reaction with hot potassiumbisulfate is. converted to 3-ethoxy-1,3-pentadiene; this product is thenreacted with benzoquinone in accordance with the. Diels-Aldercondensation procedure to produce S-methyl- 6 ethoxy 1,4,4a,5,8,8ahexahydronaphthalene 1,4 dione which on reaction with hydrogen in thepresence of Raney nickel catalyst forms 5-methyl-6-eth0xy-1,2,3,-4,4a,5,8,8a-octahydronaphthalene-1,4-dione; the latter product is thentreated with lithium aluminum hydride to form the corresponding diol,5-methyl-6-ethoxy-1,2,- 3,4,4a,5,8,Sa-octahydronaphthalene-1,4-diolwhich is hydrolyzed to produceS-methyl-6-keto-perhydronaphthalene-l',4-diol. These reactions aredescribed in detail in a copending application of one of the presentapplicants, Serial No. 216,109, filed March 16, 1951.

Portions of the novel subject matter disclosed but not claimed hereinare claimed in our copending applications, Serial No. 286,808 and SerialNo. 290,826 filed May 8, 1952, and May 29, 1952, respectively. Thefollowing examples are presented as illustrative of our. invention.

EXAMPLE 1 Preparation of 4b-methyl-7-ethylenedioxy-I,2,3,4,4a,4b,-

5,6,7,8,10,10a dodecahydrophenanthrene 1,4 diol (VIII) Into a 5 literflask equipped with a stirrer, a 1 liter dropping funnel and a sidearmwith condensor attached in distilling position, were placed 38.9 g.(0.155 mole) of4b-methyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1,4-diol-7-one(I), 40 cc. (0.645 mole.) of glycol, 2,500 cc. of ethylene dichlorideand 0.4 g. (0.002 mole) of p'toluene-sulfonie acid. This mixture was setstirring. Enough heat was applied todistill off 6 3 liters of theazeotrope of the solvent and water, formed as a by-product, dun nga3-hour period. During thisti'me an additional 1,500 cc. of ethylenedichloride was added to keep the reactants insolution. After 3 hours thereaction mixture was cooled and thoroughly shaken with 50 cc. of anaqueous 1 Normal potassium bicarbonate solution. The aqueous carbonatelayer was drawn off and twice extracted with ethylene dichloride. Allthree ethylene dichloride. extracts were then combined, dried overanhydrous magnesium sulfate and concentrated. This concentrate was.taken up. in 1 liter of acetone and concentrated until crystals justbegan to come out. Filtration of the cold acetone gives the crudecrystalline product, 4b-methyl-7-ethylenedioxy-1,-2,3.,4,4a,4b,5,,6,,7,8,10,102. dodecahydrophenanthrcne 1,4-diol whichcan be further purified. by recrystallization from acetone. The pureproduct melts. at 189 C.

EXAMPLE 2 Preparation 0]? 4bmethyl-7-ethyltznedioxy-1,2,3,4;4a,4b,--5,6,7,8,1 0,1 Oa-dodecahydrophenanthrene 1 one 4 ol (IX) and4b-methyl-7-ethylenedioxy-1,2,3,4,4a,4b,- 5,6, 7,8,10,10adodecahydrophenanth'rene 1,4 dione (X Eighty-six and five-tenths grams(0.294- mole) of 4bmethyl 7 eth-ylenedioxy 1,2,3,4,4a,4b,5,6.,7,8,10,-10a-dodecahydrophenanthrene-l,4-diol wasv dissolved in 2,130 g. (2,250cc.) (2.1.7 moles). of cyclohexanone, and 2,250, cc. of benzene. To thissolution was added 86.5 g. (0.424 mole). of aluminum isopropoxide, andthe whole was then set to reflux for 12 hours. At. the end of this time25 cc. of water was added. The coagulated aluminum hydroxide; thusformed was filtered off. The filtrate was then concentrated and dried invacuo, leaving a residue which, on trituration with petroleum ether,gave the crude crystalline product 4b-methyl-7-ethylenedioxyI,2,3,4,4a,4b,5',6,7,8,10,10a d'odecahydrophenanthrene-l-one-4-ol. Itcan be purified by recrystallization and melts at 219220 C.

The petroleum ether washes, used in the trituration, contain the product4b-methylJ-ethylenedioxy-1,2',3,4,- 4a,4b,5,6,7,.8,10,10adodecahydrophenanthrene 1,4 dione. It can. be purified byrecrystallization and melts at C.

EXAMPLE 3 Preparation of4b-methy-l-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthren2-],4,7-trione(XI) To a solution of 0.434. g. (040015 mole) of 4b-methyl- 7ethylenedioxy l,2,3.,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-1,4-dione (X) in 1.0 cc. of methanol was added 1cc. of 2.5. Normal hydrochloric acid. After refluxing this acidicsolution for 2 /2 hours, 8 cc. of water was added. All the methanol wasthen distilled and the resulting suspension extracted three times withchloroform. The three extracts were combined, dried over anhydrousmagnesium sulfate and concentrated to give thecrude product which waspurified by chromatography over alumina. The. desired product was elutedwith a mixture of ether and chloroform. The pure 4b-methyl-1,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydrophenanthrene- 1,4,7-trione meltsat 117 C.

EXAMPLE 4 Preparation of 4b-methyl-7-ethylenedioxy-I,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene 1,4-dz'one (X) by the chromiumtrioxide-pyridine oxidation of Compound IX A solution of 3.12 g. of4b-methyl-7-ethylenedioxy- 1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene- 1-one-4-ol (IX) in 30 cc. of pyridine wascombined with 3.1 g. of chromium trioxide in 30 cc. of pyridine. Thereaction flask was, stoppered, the contents mixed thoroughly and allowedto stand at room temperature overnight. The reaction mixture was pouredinto water and extracted with three portions of benzene-ether (1:1) withfiltration through diatomaceous earth to break the emulsions. Afterwashing with water, the combined organic solution was dried overanhydrous magnesium sulfate and concentrated with final drying of theresidue under high vacuum. Crystallization from ether gave Compound X,M. P. 117-121 C.

EXAMPLE 5 Preparation of 4b-methyl-7-ethylenedioxy-I,2,3,4,4a,4b,5,

6,7,8,10,10a dodecahydrophenanthrene 1,4 diol- 1,4diacetate (XIV) Thirtymilligrams of Compound XIII in a mixture of 1 ml. of pyridine and 0.5ml. of acetic anhydride was kept at 100 C. for ten minutes. Aftercooling, diluting with water and extracting with chloroform, there wasobtained Compound XIV, M. P. 160l65 C. The pure Compound XIV melted at163165 C. after several recrystallizations from ether-petroleum ethermixture.

EXAMPLE 6 Preparation of 4b-methyl-7-ethylenedioxy-1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene 1,4 diol 1' acetate (XV) A solutionof 2.00 g. of Compound VIII in 20 cc. of dry pyridine and cc. of aceticanhydride was kept at 100 C. for ten minutes. Excess acetic anhydridewas hydrolyzed with ice water, and the reaction mixture was diluted to100 cc. The crystalline product was collected on a filter, washedthoroughly with water and dried. A sample recrystallized twice fromacetone yielded pure Compound XV melting at 183.5184 C.

EXAMPLE 7 Preparation of 4b-methyl-7-ethylenedioxy-1,2,3,4,4a,4b,5,

6,7,8,10,10a dodecahydrophenanthrene 1 ol 4- one-1 -acetate (XVI) Twograms of chromium trioxide was dissolved in cc. of dry pyridine withcooling. To the resulting suspension of orange complex was added asolution of 2.00 g. of Compound XV in 20 cc. of dry pyridine. Thereaction flask was stoppered, the contents were mixed thoroughly byagitation and allowed to stand overnight. The reaction mixture waspoured into 100 cc. of water and extracted with three 100 cc. portionsof benzene. Filtration of the emulsions through diatomaceous earth wasnecessary to obtain separation of the extracts. The benzene solutionswere combined, washed with water, dried over anhydrous magnesium sulfateand concentrated. After drying under high vacuum to remove pyridine, theresidue was crystallized from ether. Two

recrystallizations from ether gave Compound XVI melting at l43144.5 C.

EXAMPLE 8 Preparation of 4b-methyl-7-ethylenedioxy-1,2,3,4,4a,4b,5,

6,7,8,I0,I0a dodecahydrophenanthrene 1 ol 4- one (XVII) A solution of0.726 g. of Compound XVI in 10 cc. of 0.25 N potassium carbonate in 75%methanol was refluxed for twelve minutes. Water was added and themethanol was removed in vacuo. Organic material was collected inchloroform and the chloroform solution was dried and evaporated to yielda crystalline product, M. P. 137l40 C. On recrystallization from ether,Compound XVII was obtained, melting at 142143 C.

A mixture with starting acetate melted below 130 C.

Upon passage over alkaline alumina, Compound XVII was recoveredunchanged.

Acetylation with acetic anhydride-pyridine by the standard proceduregave the acetate precursor Compound XVI.

8 EXAMPLE 9 Preparation of 4b-methyl-7-ethylenedioxy-1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene 1,4 dione (XVIII) and4b-methyl-7-ethylenedioxy-I,2,3,4,4a,4b, 5,6,7,8,10,10adodecahydrophenanthrene 1,4 dione (X), a stereoisomeric form of XVIII Asolution of 0.182 g. of Compound XVII in 2 cc. of pyridine was oxidizedwith 0.20 g. of chromium trioxide in 2 cc. of pyridine at roomtemperature overnight. After dilution with water and extraction withbenzene, there was obtained a non-crystalline product. On standing, anether solution of this material deposited crystals, M. P. C.

Several recrystallizations from ether yielded Compound XVIII, M. P.146-8 C.

The first ether mother liquor was passed over alkaline alumina. CompoundX, M. P. 118-1195 C. was obtained; mixed melting point with anothersample of Compound X, 118.5120 C.

EXAMPLE 10 Preparation of compounds X, IX, XVII and XVIII by thechromium trioxide-pyridine oxidation of Compound VIII Three grams of4b-methyl-7-ethylenedioxy-1,2,3,4,4a, 4b,5,6,7,8,10,10adodecahydrophenanthrene 1,4 diol (VIII) in 30 cc. of dry pyridine wascombined with 3.0 g. of chromium trioxide in 30 cc. of pyridine andallowed to stand at room temperature overnight. Dilution with waterfollowed by extraction with benzene-ether, washing, drying concentrationand vacuum drying gave 2.90 g. of crude, non-crystalline product.

When this material was chromatographed over 90 g. of alkaline alumina,the benzene eluate gave Compound X, M. P. 113-118 C. with ether andether-chloroform (1:1), there was eluted first Compound IX, M. P.216-219" C. and finally Compound XVII, M. P. 130-138" C.

It was possible to obtain Compound XVIII from Compound VIII byreoxidation of the crude product obtained above with chromiumtrioxide-pyridine. Chromatography of this second stage oxidation productover alkaline alumina gave Compound X.

EXAMPLE 11 Preparation of 4b methyl 7 ethylenedioxy 1,2,3,4,4a,-4b,5,6,7,8,10,10a dodecahydrophenanthrene 1 ol- 4-one (XIX) A solutionof 98 mg. of Compound XVII in 5 cc. of 0.5 N potassium carbonate in 75methanol was heated at reflux for three hours. Methanol was distilledand the product was collected in chloroform. Evaporation of the solventgave a crystalline product, M. P. l131l6 C. Two recrystallizations fromether yielded Compound XIX melting at 117.5118.5 C.

EXAMPLE 12 Preparation of 4b methyl 7 ethylenea'ioxy 1,2,3,4,4a,-4b,5,6,7,8,10,10a dodecahydrophenanthrene 1,4- dione (XX), astercoisomeric form of Compound X To the chromium trioxide-pyridinecomplex from 0.30 g. of chromium trioxide and 3 cc. of pyridine wasadded a solution of 270 mg. of Compound XIX in 3 cc. of pyridine. Themixture was left at room temperature for two hours and then was dilutedwith water and extracted with benzene. After removal of the solvent andvacuum drying of the residue, crystallization from ether gave productmelting at -170 C. along with a small amount of unchanged startingmaterial. The product was recrystallized 3 times from ether to obtainpure Compound XX, M. P. 171-172 C.

Preparation of 4b methyL IaZ'JAAZf bI-I,61111 4dodecahydrophenanthrene-I -ol-4,7-di0ne (XXI) To a solution of 227 mg.of Compound XVII in cc. of acetone was added one drop of hydrochloricacid. The solution was boiled for fifteen minutes and then diluted withwater and the acetone distilled in vacuo. The aqueous suspension wasextracted with chloroform and the chloroform solution was dried andevaporated to give crystalline Compound XXI, M. P. 118123 C. Threerecrystallizations from. ether werev usedto. prepare. the pure product,M. P: 1'26-127,"' C.

EXAMPLE 14.

Preparation 0]. lb-methyl l,2,3,4,4a,4b,5, 6,7,9,10,10a-

dodecahydrophenanthrene 1,4,7 Q trione (XXII), a stereoisomericmodification of cempaund XI A solution of 140 mg. of Compound XXI in 5cc. of 90% acetic acid was treated portionw-ise with cooled 1.4 cc. of10% chromic acid in 90%,. acetic: acid. After. standing: at roomtemperature for one: and a half hours, the reaction mixture was dilutedwith water: and extracted with four portions of chloroform. Thechloroform solution was neutralized with excess sodium bicarbonate solution, washed with water and dried over anhydrous magnesium sulfate.Evaporation of the solvent gave crystalline product melting at 160164 C.Three recrystallizations from benzene-ether (1:1) gave Compound XXIImelting at 164-166 C.

EXAMPLE Preparation of Compound XI by the isomerization of Compound XXIITwenty-three milligrams of XXII in benzene solution was absorbed on twograms of alkaline alumina. After one hour, the material was eluted withether-chloroform (1:1) giving crystals melting at 98-1 10 C. Tworecrystallizations from ether gave 4b-methyl-1,2,3,4a,4b,5,6,7- 9,10,10adodecahydrophenanthrene 1,4,7 trione (XI), melting point and mixedmelting point of this product with another sample of Compound XI,117117.5 C.

EXAMPLE 16 Preparation of 4b methyl 7 ethylenedioxy l,2,3,4,4a,-

4b,5,6,7,8,10,10a dodecahydrophenanthrene 1,4 diol (XIII), astereoisomeric form of Compound VIII To 0.5 gram of lithium aluminumhydride in cc. of dry tetrahydrofuran was slowly added with stirring asolution of 0.180 g. of Compound X in dry tetrahydrofuran. Afterstirring for one hour at room temperature, 2.0 cc. of water was addeddropwise and the precipitated inorganic salts separated by filtration.Tetrahydrofuran was distilled leaving a crystalline residue. Afterseveral recrystallizations from acetone the product, Compound XIII,melted at 198-1995 C.

Various changes and modifications may be made in carrying out thepresent invention without departing from the spirit and scope thereof.Insofar as these changes and modifications are within the purview of theannexed claims, they are to be considered as part of our invention.

We claim:

1. 4b methyl 1,2,3,4,4a,4b,5,6,7,9,10,10adodecahydrophenanthrene-1,4,7-trione.

2. The stereoisomeric form of 4b-methyl-1,2,3,4,4a,4b,- 5,6,7,9,10,10adodecahydrophenanthrene 1,4,7 trione melting at about 117-117.5 C.

3. The stereoisomeric form of 4b-methyl-1,2,3,4,4a,4b,- 5,6,7,9,10,10adodecahydrophenanthrene 1,4,7 trione melting at about 164-166 C.

4. 4b methyl 7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,-8,10,10a-dodecahydrophenanthrene-1,4-dione.

5. The stereoisomeric form of 4b-methyl-7-ethylenedithrene-l-A-dionemelting; at about l7-1-17-2' C.

and 7'-enol' ether and 7'-ketal derivatives thereof.

8. The process for preparing 4b methyl 1,2,3',4,4a',- 4b,5,6,7,9,1 0,10adodecahydrophenanthrene 154,7 tri-- one which comprises reacting 4bmethyl 7 ethylenedi'oxy I-,2,3 ,4,4a,4b ,5 ,6 ,7,8,10g10adodecahydrophenanthrene 1,4 diol with aluminumisopropoxide andcyclinhexanone, recovering 4b methyl 7 ethylenedioxy 1',2,3,4,4a,4b,5-,6,7,8',10,1 0a dodecahydrophenanthrene 1,4 dione from theresulting reaction, and hydrolyzing said dione by heating with an acid.

9. The process for preparing 4b methyl l,2,3,4,4a,- 4b,5,6,7,9,10,10adodecahydrophenanthrene 1,4,7 trione which comprises reacting 4b methyl7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene 1,4diol with pyridine-chromium trioxide complex in pyridine, recovering 4bmethyl 7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene 1,4 dione from the resulting reaction,intimately contacting said dione with an inorganic base, and hydrolyzingthe resulting product by heating with an acid.

10. The process for preparing 4b methyl 1,2,3,4,4a,- 4b,5,6,7,9,10,10adodecahydrophenanthrene 1,4,7 trione which comprises reacting 4b methyl7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene 1,4diol with pyridine-chromium trioxide complex in pyridine, recovering 4bmethyl 7 ethylenedioxy- 1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene-1-ol-4-one from resulting reaction, hydrolyzingthe recovered product by heating with an acid, intimately contacting thehydrolyzed product with chromium trioxide, and reacting the resultingoxidized product with an inorganic base.

11. The process for preparing 4b methyl 1,2,3,4,4a,- 4b,5,6,7,9,10,10adodecahydrophenanthrene 1,4,7 trione which comprises reacting a memberfrom the group consisting of 7-enol ether and 7- ketal derivatives of acompound of the formula with an oxidizing agent, and hydrolyzing theresulting reaction product by heating with an acid.

12. The process for preparing a compound of the formula:

which comprises reacting 4b methyl 7 ethylenedioxy1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene 1,4 diol withacetic anhydride in the presence of pyridine, oxidizing a pyridinesolution of the resulting acetylated product with pyridine-chromiumtrioxide complex, to produce the corresponding 1,4-diol-1-acetate,hydrolyzing the resulting oxidized product with potassium carbonate,reoxidizing the resulting hydrolyzed product with pyridinechromiumtrioxide complex in pyridine solution, and hydrolyzing the resultingoxidized product by heating with an acid.

13. The process for preparing a stereoisomeric form of 4b methyl1,2,3,4,4a,4b,5,6,7,9,10,1021 dodecahydrophenanthrene 1,4,7 trionehaving a melting point of about 117 C. which comprises reacting astereoisomeric form of this trione having a melting point of about164166 C. with an inorganic base.

14. The process for preparing a stereoisomeric form of 4b methyl1,2,3,4,4a,4b,5,6,7,9,1O,10a dodecahydrophenanthrene 1,4,7 trione havinga melting point of about 117 C. which comprises reacting astereoisomeric form of this trione having a melting point of about164166 C. with alkaline alumina.

15. The stereoisomeric form of 4b methyl 7 ethylenedioxy1,2,3,4,4a,4b,5,6,7,8,10,1021 dodecahydrophenanthrene 1,4 dione meltingat about 146-148 C.

16. The process which comprises reacting a compound from the groupconsisting of 7-enol ether and 7-ketal derivatives of a compound of theformula with an oxidizing agent to produce the corresponding derivativesof 4b methyl 1,2,3,4,4a,4b,5,6,7,9,10,10a dodecahydrophenanthrene 1,4,7trione.

References Cited in the file of this patent UNITED STATES PATENTS2,302,636 Koster et a1 Nov. 17, 1942 2,617,828 Sarett et a1 Nov. 11,1952 FOREIGN PATENTS 235,431 Switzerland Apr. 16, 1945 235,485Switzerland Apr. 16, 1945 235,487 Switzerland Apr. 16, 1945

12. THE PROCESS FOR PREPARING A COMPOUND OF THE FORMULA: